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Palmitoylethanolamide in neuropathic sciatic pain: clinical results


Palmitoylethanolamide (PEA) is an natural and endogenous compound. It is a fatty acid amide and present in many foodstuffs as well as in the human body. In Europe PEA is available as a nutraceutical (dietfood for medical purposes)  in Italy and Spain under the brandname een PEA-houdend product and in the Netherlands and elsewhere as a foodsupplement under the brandname PeaPure. 

PeaPure has the advantage of not containing farmaceutical and chemical excipients, nor sorbitol (as present in een PEA-houdend product and other PEA products).

In 2010 a Spanish publication described clinical meaningful effects of the treatment of lumbosciatic pain with palmitoylethanolamide, PEA. These results were published in Dolor (2010;25:35-42) and were based on a double blind placebo contriolled study.

TWe conducted a furher analysis of the Numbers Needed to Treat we presented at the SIAARTI in 2011 for around 1000 pain specialists, the efficacy of PEA based on the NNT analysis we presented was impressive: 1.5! For details see link.

The presentation at the SIAARTI was moderated and introduced by professor G. Varrassi. 

In various different clinical nerve compression studies, conducted up to 2011, a total of more than 1300 patients  wre treated all confirming positive effects for PEA in sciatic pain (see under)  

PEA is a safe compound, with virtually no side effects, and a robust efficacy (NNT=1.5, see graph: NNT at week 3 for 50% pain reduction on NRS). 


Palmitoylethanolamide (PEA) effective in lumbosciatic pain 

The study was double blind, placebo controlled and two different dosages of pure palmitoylethanolamide were evaluated in a three weeks treatment regime.[1] Two different doses were compared, 300 mg and 600 mg daily and a third study arm was the placebo arm. As far as we could analyse the compound used was pure palmitoylethanolamide, and not a branded formulation.

Six hundred and thirty-six patients patients suffering from lumbosciatic pain due to radicular compression of the sciatic nerve and discopathy were included. 

Primary endpoint was measured via the the visual analogue scale (VAS), in order to quantify the intensity of the pain, and by the Roland- Morris disability questionnaire (RDQ) to evaluate the quality of life. There were only few dropouts; seventeen patients. At the end of the three weeks treatment period both the pain reduction and the quality of life were significantly different between the three treatment groups (ANOVA; p < 0.001), and the daily dose of 600 mg was the most effective dose.

The decrease on the VAS was in the highest dose group a reduction from 7.1 to 2.1, which is more than 50% pain reduction, this is in general considered as a robust clinical response. In the placebo arm the painscore did decrease from 6.6 to 4.6.  

Comments on the efficacy and safety PEA

The study seems to indicate that the PEA has a relative quick action of onset as an analgesic drug in the treatment of the Lumbosacral Discogenic Pain Syndrome, or sciatic pain. Within 3 weeks both the 300 mg as well as the 600 mg dose decreased pain significantly more efficient as compared to placebo.

This is the first clinical study of sufficient magnitude, more than 600 patients entered the study, which was conducted in a number of Italian medical sites, supporting the efficacy of a natural supplement, PEA in a difficult to treat neuropathic pain syndrome.

Side effects were minor and this makes PEA a quite attractive molecule and a promising treament alternative, as side effects mostly limit the use of many analgesics in neuropathic pain, such as in amitriptyline and pregabaline. een PEA-houdend product therefore might become an interesting alternative in the treatment of neuropathic pain.

In our own clinic we started working with PEA some time ago, and in several patients suffering from neuropathic pain we found robust analgesic effects, without any side effects. Our dose regime is 1200 mg/day to start with.

In the table a summary of clinical trials in nerve compression syndromes, were palmitoylethanolamide was tested. All studies supported its efficacy and safety.













Here a patient presentation of a MD suffering from severe sciatic pain due to a herniation L4/L5, not responding to Lyrica, and being a full responder on palmitoylethanolamide. 


PEA is effective and safe in the elderly

Analgesic treatments with a low side effect profile such as palmitoylethalonamide are quite relevant for elderly patients, due to its benign side-effect profile. [2][3][4][5].

Especially the absence of sedative side effects is important. A great number of elderly patients have been treated without side effect or dose limiting problems, or interaction problems. Furthermore, combination therapy with pregabalin seems feasable and even clinically useful. [6]

Within the context of clinical studies more then 350 elderly patients have been treated with palmitoylethanolamide without side effect problems, and also in our hands, we did not detect any clinical relevant side effects, even not in a patient aged 90. A database analysis in 2011 resulted in the following numbers of elderly patients treated with palmitoylethanolamide:

  • 111 patients between 65 and 70 years old
  • 116 patientsbetween 71 and 75 y.o.
  • 63 patients between 76 and 80 y.o.
  • 45 patients between 81 and 85 y.o.
  • 20 patients between 86 and 90 y.o. 

PEA seems to have a great many biological effects, and might be quite interestng for a number of varying disorders. Recently a review summerized all biological actions of PEA, and we quote:[7]


  • Acute pain ↓
  • Inflammatory pain ↓
  • Neuropathic pain ↓


  •  Mast cell activation ↓
  •  iNOS expression ↓
  •  COX-2 expression ↓
  •  Neutrophil influx ↓


  •  Convulsions ↓
  •  Excitotoxicity ↓


  • Incidences of acute  respiratory diseases ↓
Studie 2012:
C Morera Domínguez, A Díaz Martín, F Garibo Ferrer, MA Ibáñez Puertas, A Leal Muro, JC Martí González, J Pombo Prieto, and I Rosselló TabernaN-palmitoylethanolamide in the treatment of neuropathic pain associated with lumbosciatica.
Pain Management, March 2012, Vol. 2, No. 2 , Pages 119-124 

Prof. dr. Jan M. Keppel Hesselink MD, and David J. Kopsky MD December 2010, revision march 2012, JMKH


[1] G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor | 2010, 25:35-42

[2] Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.

[3] Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. | Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. | Pain Med. | 2010 May;11(5):781-4. Epub 2010 Mar 22.

[4] Petrosino S, Iuvone T, Di Marzo V. | N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities. | Biochimie. | 2010 Jun;92(6):724-7. Epub 2010 Jan 21.

[5] Phan NQ, Siepmann D, Gralow I, Ständer S. | Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. | J Dtsch Dermatol Ges. | 2010 Feb;8(2):88-91. Epub 2009 Sep 10.

[6] P,Deslo. Combination of pregabalin and palmitoylethanolamide (PEA) for neuropathic pain treatment. | Pathos, 2010, 17,4:9-14

[7] LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D. | The search for the palmitoylethanolamide receptor. | Life Sci. | 2005 Aug 19;77(14):1685-98.